Crol contributes to PRE-mediated repression and Polycomb group proteins recruitment in Drosophila.
Crol contributes to PRE-mediated repression and Polycomb group proteins recruitment in Drosophila.
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DOI：
10.1093/nar/gkad336
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发表时间：
2023-07-07
影响因子：
14.9
通讯作者：
Chetverina, Darya
中科院分区：
文献类型：
--
作者：
Erokhin, Maksim;Brown, J. Lesley;Lomaev, Dmitry;Vorobyeva, Nadezhda E.;Zhang, Liangliang;Fab, Lika, V;Mazina, Marina Yu;Kulakovskiy, Ivan, V;Ziganshin, Rustam H.;Schedl, Paul;Georgiev, Pavel;Sun, Ming-an;Kassis, Judith A.;Chetverina, Darya
多梳族 (PcG) 蛋白是基本的表观遗传调节因子，可控制多细胞生物中靶基因的抑制状态。悬而未决的问题之一是定义 PcG 募集到染色质的机制。在果蝇中，PcG 募集的关键作用被认为属于与 Polycomb 反应元件 (PRE) 相关的 DNA 结合蛋白。然而，目前的数据表明并非所有 PRE 结合因子都已被识别。在这里，我们报告了转录因子 Crooked Legs (Crol) 的鉴定，它是一种新型的 PcG 招募因子。 Crol 是一种 C2H2 型锌指蛋白，可直接与富含多聚 (G) 的 DNA 序列结合。 Crol 结合位点的突变以及 Crol CRISPR/Cas9 敲除会减弱转基因中 PRE 的抑制活性。与其他 PRE-DNA 结合蛋白一样，Crol 与 H3K27me3 结构域内部和外部的 PcG 蛋白共定位。 Crol 敲除会损害部分位点上 PRC1 亚基 Polyhomeotic 和 PRE 结合蛋白 Combgap 的募集。 PcG 蛋白结合的减少伴随着靶基因转录失调。总体而言，我们的研究确定 Crol 是 PcG 招募和表观遗传调控中新的重要参与者。
The Polycomb group (PcG) proteins are fundamental epigenetic regulators that control the repressive state of target genes in multicellular organisms. One of the open questions is defining the mechanisms of PcG recruitment to chromatin. In Drosophila, the crucial role in PcG recruitment is thought to belong to DNA-binding proteins associated with Polycomb response elements (PREs). However, current data suggests that not all PRE-binding factors have been identified. Here, we report the identification of the transcription factor Crooked legs (Crol) as a novel PcG recruiter. Crol is a C2H2-type Zinc Finger protein that directly binds to poly(G)-rich DNA sequences. Mutation of Crol binding sites as well as crol CRISPR/Cas9 knockout diminish the repressive activity of PREs in transgenes. Like other PRE-DNA binding proteins, Crol co-localizes with PcG proteins inside and outside of H3K27me3 domains. Crol knockout impairs the recruitment of the PRC1 subunit Polyhomeotic and the PRE-binding protein Combgap at a subset of sites. The decreased binding of PcG proteins is accompanied by dysregulated transcription of target genes. Overall, our study identified Crol as a new important player in PcG recruitment and epigenetic regulation.
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影响因子：
3.9
作者：
Erokhin M;Davydova A;Parshikov A;Studitsky VM;Georgiev P;Chetverina D
通讯作者：
Chetverina D
影响因子：
64.5
作者：
Czermin, B;Melfi, R;Pirrotta, V
通讯作者：
Pirrotta, V
DOI：
10.1038/s41580-021-00398-y
发表时间：
2021-12
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Blackledge NP;Klose RJ
通讯作者：
Klose RJ
DOI：
10.1073/pnas.1515276112
发表时间：
2015-12-01
影响因子：
11.1
作者：
Erokhin, Maksim;Elizar'ev, Pavel;Chetverina, Darya
通讯作者：
Chetverina, Darya
影响因子：
3.3
作者：
Brown, J. Lesley;Kassis, Judith A.
通讯作者：
Kassis, Judith A.